Fig. 1.

dsDNA interacts with cyclic GMP–AMP synthase (cGAS), which converts ATP and GTP to the second messenger 2′3′ cyclic GMP–AMP (cGAMP). In the endoplasmic reticulum, cGAMP binds and activates STING, leading to activation and phosphorylation of IRF3 by TANK-binding kinase 1. IRF3 forms homodimers and trans-locates into the nucleus to induce type I IFN expression. The RNA sensing pathway is also involved in AGS as a result of activation of the MDA5/MAVS pathway. STING stimulator of interferon genes, IRF3 interferon regulatory transcription factor 3, IFN interferon, AGS Aicardi–Goutières syndrome, MDA5 melanoma differentiation-associated gene 5, MAVS mitochondrial antiviral signaling